Real-life use of cabozantinib as front-line therapy in metastatic renal cell carcinoma: The CabFRONT (Meet-URO 24) study.
Authors: Pierangela Sepe, Giuseppe Fotia, Giandomenico Roviello, Marco Maruzzo, Brigida Anna Maiorano, Marilena Di Napoli, Alessia Mennitto, Mariella Sorarù, Matteo Santoni, Elisa Zanardi, Vincenza Conteduca, Luca Galli, Enrico Bronte, Ugo De Giorgi, Lorena Incorvaia, Francesco Atzori, Maria Cossu Rocca, Paolo Andrea Zucali, Giuseppe Procopio, Elena Verzoni
Journal: Journal of Clinical Oncology (2023)

e16539 Background: Cabozantinib is approved as first-line therapy for patients with intermediate-poor risk metastatic renal cell carcinoma (mRCC); however translating results from pivotal trials to an unselected real-world population remains a concern. Methods: CabFRONT is a retrospective observational multicentre Italian Network for Research in Urologic-Oncology (Meet-URO) study of a real-life population of treatment-naïve patients with intermediate-poor mRCC treated with cabozantinib as per clinical practice between September 2019 and September 2022. Results: 209 patients were enrolled. Median age was 65 years (36 - 85). 158 patients (76%) started with a dose of 60 mg, while 51 (24%) started with a dose of 40 mg. 140 patients (67%) were classified as intermediate and 69 (33%) as poor risk according to IMDC risk model. Clear-cell represented the most common histotype (172/209), followed by papillary (19/209), chromophobe (6/209) and NOS (4/209). Sarcomatoid features were present in 29 patients (14%). Lungs were the most frequent metastatic site, [137 (65%) patients], followed by lymph nodes [115 (55%)], and bones [72 (35%)]. 33 (16%) patients presented brain metastases. At a follow-up of 23 months (mo), the median progression-free survival (mPFS) was 9.6 mo (95% CI, 7.63-10.9 mo) and the median overall-survival was 21 mo (95% CI, 14-30 mo). As best overall response, 7 patients achieved a complete response, 73 a partial response and 77 stable disease for an objective response rate (ORR) of 38% and a disease control rate (DCR) of 75%. ORR for intermediate and poor population was respectively 29% and 10%, DCR was 56% for intermediate risk and 20% for poor risk population. mPFS for intermediate and poor population was respectively 12.73 and 5.27 mo (p &lt; 0.0001). mPFS for intermediate with 1 risk factor was 17.2 and for intermediate with 2 risk factors was 9.7 mo (p 0.0033). Subsequent antineoplastic treatments were received by 41% (86/209) of patients. Subsequent nivolumab was received by 87% of patients. 191 patients (91%) reported at least 1 grade (G) 1 to 2 adverse event (AE). The most common G1 to G2 AEs were fatigue (113 [60%]), mucositis (100 [52%]), hand-foot syndrome (HFS) (91 [47%]), diarrhoea (79 [41%]), hypertension (67 [35%]), and hypothyroidism (60 [31%]). 78 G3 AEs ere reported: the most common were fatigue (19 [24%]) and diarrhoea (18 [23%]). Permanent discontinuations from the study owing to AEs was observed in 7 patients: three for G3 diarrhea, one of which manifested also G3 renal injury, two for G3 asthenia, one for G3 HFS and one for G3 mucositis. At least 131 patients (63%) required a dose reduction and 86 (41%) required a transitory interruption to manage toxic effects. Conclusions: Our data confirmed that front-line Cabozantinib is effective and safe in an unselected real-life population of patients with intermediate-poor mRCC, including non-clear cell histologies.